1 Introduction

Diseases with a genetic basis are usually diagnosed by looking for causal mutations in a panel of genes specifically associated with the disease. Gathering all phenotypes associated with the genes in a panel delivers a general phenotype-level description beyond the disease under study. For the purpose of improving genetic diagnosis, we need methods to evaluate the gene level phenotypic similarity between diseases and to identify differential phenotypes between the gene sets associated. Comparative phenotypic similarity analysis between gene panels can demonstrate common pathophysiology and help to create genetic links between diseases through their gene sets. PhenoExam works on this principle by integrating databases like The Human Phenotype Ontology (HPO) and The Mouse Genome Database (MGD).

PhenoExamWeb is an R package that performs (1) phenotype enrichment analysis on a gene set, (2) measures statistically significant phenotype similarities between gene sets and (3) detects significant differential phenotypes for them. Phenotypic Similarity between two groups of genes is performed by assessing the statistical significance of the Phenotypic Overlap Ratio (POR) between those (i.e. the number of common phenotypes between the gene sets). PhenoExamWeb uses the HPO, MGD, and CRISPRbrain databases.

In this tutorial, we applied PhenoExamWeb to the detection of differential phenotypes between gene sets by comparing two genetic diseases with similar symptoms: juvenile Parkinson disease (PD) with 35 genes and early onset dystonia (EOD) with 50 genes from Genomics England PanelApp.

2 Phenotype Enrichment Analysis in Parkinson Disease genes

First, we are going to do a phenotype enrichment analysis with PhenoExamWeb in Parkinson gene set.

It is interesting to determine which are the significant phenotypes in a given set of gene G. In order to calculate whether a gene set G shows enrichment in a given phenotypic term p, we calculate the number of genes g in a gene set G associated with the phenotypic term p, on the other hand, we calculate the number of genes in the reference database gdb associated with that phenotypic term p. The total universe of genes in the database GDB and the number of genes in the given set of genes G are taken into account. With this data we use a hypergeometric distribution. Where the population size is GDB, G is the size of the sample drawn, gdb is the number of items in the original population that belong to the desired category (to phenotype p in our case) and g is the number of items in the sample that belong to that category. Any phenotype with p < 0.05 will be enriched in the G gene set. We compute this for each phenotypic term p in a gene set G.

2.1 Parkinson Phenotype Enrichment Analysis

We select the juvenile Parkinson disease (PD) gene set with 35 genes from Genomics England PanelApp (G2PML package) We show the Phenotype Enrichment Analysis for Parkinson Disease genes from GenomicEngland made in all databases with PhenoExamWeb (HPO, MGD and CRISPRBrain):

# Get the panels
paneles <- getPanelsFromPanelApp()

# Get PD panel
parkinsonpanel<- getPanelFromPanelApp(disorder = "Neurology and neurodevelopmental disorders" , panel = "Parkinson Disease and Complex Parkinsonism")

parkinsonpanelf <- filter(parkinsonpanel, parkinsonpanel$LevelOfConfidence == "HighEvidence")

# Get PD high evidence genes (note that is a vector)
parkinsongenes <- parkinsonpanelf$GeneSymbol

# Get dystonia panel
dystonia <- getPanelFromPanelApp(disorder = "Neurology and neurodevelopmental disorders" , panel = "Early onset dystonia")

dystoniapanel <- filter(dystonia, dystonia$LevelOfConfidence == "HighEvidence")

# Ges dystonia genes
dystoniagenes <- dystoniapanel$GeneSymbol

It is important have the genes in a vector.

Now we can use PhenoEnrichGenes function:

parkinsonenrich <- PhenoEnrichGenes(genes= parkinsongenes, database = "ALL", plotn = 25) # For all database at the same time
parkinsonenrichmp <- PhenoEnrichGenes(genes= parkinsongenes, database = "MGD", plotn = 25) # For MGD
parkinsonenrichcrb <- PhenoEnrichGenes(genes= parkinsongenes, database = "CRB", plotn = 25) # For CRB

We observe in this table the 20 most enriched phenotypic terms:

 kbl(parkinsonenrich$htmltabla[1:20,], escape = F, digits = 1000, align = "c", format = "html", row.names = F) %>%
  kable_material_dark()
term_id term_name adjust_pvalue genes_associated_in_db gene_overlap overlap_ratio pvalue common_genes
HP:0002067 Bradykinesia 1.870582e-60 97 29 (29/97) 3.081683e-63 PLA2G6, PRKRA, ATP1A3, SYNJ1, LYST, FBXO7, CSF1R, DNAJC6, DCTN1, C19ORF12, RAB39B, FTL, GBA, GCH1, WDR45, PARK7, MAPT, PRKN, LRRK2, PANK2, SLC30A10, SLC6A3, VPS35, SNCA, SPR, ATP13A2, TH, SLC39A14, PINK1
HP:0001300 Parkinsonism 2.297659e-51 98 26 (26/98) 3.785269e-54 PLA2G6, PRKRA, ATP1A3, SYNJ1, FBXO7, DNAJC6, DCTN1, C19ORF12, RAB39B, FTL, GBA, GCH1, GRN, WDR45, MAPT, PRKN, PANK2, SLC30A10, SLC6A3, VPS35, SNCA, VPS13A, ATP13A2, TH, SLC39A14, PINK1
HP:0002063 Rigidity 1.628465e-46 144 26 (26/144) 2.682809e-49 PLA2G6, SYNJ1, LYST, FBXO7, CSF1R, DNAJC6, DCTN1, C19ORF12, TUBB4A, FTL, GBA, GCH1, WDR45, PARK7, MAPT, PRKN, LRRK2, PANK2, SLC30A10, SLC6A3, VPS35, SNCA, SPR, ATP13A2, TH, PINK1
HP:0001337 Tremor 7.767941e-41 343 28 (28/343) 1.279727e-43 PLA2G6, SYNJ1, LYST, FBXO7, DNAJC6, DCTN1, C19ORF12, TUBB4A, FTL, GBA, GCH1, WDR45, PARK7, MAPT, PRKN, LRRK2, PANK2, SLC30A10, OPA3, SPG11, SLC6A3, SNCA, SPR, VPS13A, ATP13A2, TH, SLC39A14, PINK1
C0752105 Parkinsonism, Juvenile 3.339899e-33 30 15 (15/30) 2.402805e-35 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, SYNJ1, PARK7, ATP13A2, FBXO7, SLC30A10, PINK1, LRRK2
HP:0002172 Postural instability 3.665796e-32 59 17 (17/59) 6.039203e-35 PLA2G6, ATP1A3, SYNJ1, FBXO7, CSF1R, DNAJC6, C19ORF12, GBA, PARK7, MAPT, PRKN, LRRK2, SLC30A10, VPS35, SNCA, ATP13A2, PINK1
HP:0000338 Hypomimic face 7.629024e-32 32 15 (15/32) 1.256841e-34 PLA2G6, ATP1A3, SYNJ1, FBXO7, DNAJC6, FTL, GBA, LRRK2, SLC30A10, SLC6A3, VPS35, SNCA, SPR, ATP13A2, SLC39A14
HP:0001332 Dystonia 1.946153e-30 323 23 (23/323) 3.206184e-33 PLA2G6, ATP1A3, SYNJ1, FBXO7, DNAJC6, C19ORF12, TUBB4A, FTL, GBA, GCH1, WDR45, PARK7, MAPT, PRKN, LRRK2, PANK2, SLC30A10, VPS35, SNCA, SPR, VPS13A, ATP13A2, PINK1
C0242423 Ramsay Hunt Paralysis Syndrome 6.798872e-28 28 13 (13/28) 4.891275e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752097 Autosomal Dominant Juvenile Parkinson Disease 6.798872e-28 28 13 (13/28) 4.891275e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752098 Autosomal Dominant Parkinsonism 6.798872e-28 28 13 (13/28) 4.891275e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752100 Autosomal Recessive Parkinsonism 6.798872e-28 28 13 (13/28) 4.891275e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752101 Parkinsonism, Experimental 6.798872e-28 28 13 (13/28) 4.891275e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C0752104 Familial Juvenile Parkinsonism 6.798872e-28 28 13 (13/28) 4.891275e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
C1868675 PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE 6.798872e-28 28 13 (13/28) 4.891275e-30 ATP1A3, DCTN1, GBA, MAPT, PRKN, SNCA, TH, PRKRA, PARK7, ATP13A2, SLC30A10, PINK1, LRRK2
HP:0001347 Hyperreflexia 4.463175e-25 554 23 (23/554) 7.352842e-28 PLA2G6, PRKRA, SYNJ1, FBXO7, CSF1R, DNAJC6, DCTN1, C19ORF12, FTL, GBA, GCH1, GRN, PARK7, MAPT, PRKN, LRRK2, PANK2, OPA3, SPG11, SNCA, SPR, ATP13A2, PINK1
HP:0001260 Dysarthria 4.925506e-25 459 22 (22/459) 8.114507e-28 PLA2G6, PRKRA, ATP1A3, SYNJ1, FBXO7, CSF1R, DNAJC6, DCTN1, C19ORF12, RAB39B, TUBB4A, FTL, GBA, MAPT, PANK2, SLC30A10, OPA3, SPG11, SNCA, SPR, VPS13A, ATP13A2
HP:0000726 Dementia 1.215767e-24 150 17 (17/150) 2.002911e-27 FBXO7, DCTN1, C19ORF12, RAB39B, TUBB4A, FTL, GBA, GRN, WDR45, MAPT, LRRK2, PANK2, VPS35, SNCA, VPS13A, ATP13A2, PINK1
HP:0002548 Parkinsonism with favorable response to dopaminergic medication 5.590449e-24 19 11 (11/19) 9.209965e-27 PLA2G6, FBXO7, GBA, GCH1, PARK7, MAPT, LRRK2, VPS35, SNCA, ATP13A2, TH
HP:0000741 Apathy 2.025854e-23 48 13 (13/48) 3.337485e-26 SYNJ1, DNAJC6, DCTN1, GBA, GRN, PARK7, MAPT, PRKN, LRRK2, VPS35, SNCA, ATP13A2, PINK1

We get a plot with the 25 most enriched phenotypic terms. For example, we observe some interesting phenotypes such as Bradykinesia, Parkinsonism, Tremor and Lewy bodies.

parkinsonenrich$graph

We can obtain the same plot for CRB terms, in this case we don’t have any enrichment phenotype but we can see the genes associated with these phenotypes. For example, we can see the association with reactive oxygen species in glutamatergic neuron in these genes (ATP1A3, FBXO7, MAPT, OPA3, VPS35 and WDR45).

parkinsonenrichcrb$graph

We can get the same plot for MP terms. For example, we observe some interesting phenotypes such as abnormal gait, neuron degeneration, astrocytosis, loss of dopaminergic neuron and lipofuscinosis.

parkinsonenrichmp$graph

3 Comparator Phenotype analysis between Parkinson and Dystonia

We use RandomComparePheno function.

PhenoExam can compare the phenotype analysis of two gene sets in order to determine the similarity of phenotypes and find the phenotypic differences that make each gene set unique. In this case we are going to compare Parkinson genes with Dystonia genes.

comparareparkdis <- RandomComparePheno(parkinsongenes,dystoniagenes,database = "ALL", nulltestnumber = 1000)

First, we get a message with the summary of the analysis:

comparareparkdis$phenomessage
## [1] "Gene set2 and gene set1 shared 1104 phenotypic terms (out of 2336 unique phenotypic terms in both), that yields a Relaxed Phenotypic Overlap Ratio (RPOR) of 0.473 (p < 0.000999). They shared 140 significant phenotypic terms (out of 267 unique significant phenotypic terms in both), that yields a Phenotypic Overlap Ratio (POR) of 0.524 (p < 0.000999). Phenotype relevance association analysis for gene sets (i.e. whether the shared phenotypes are similar in relevance, i.e. in the number of genes associated with them, within each gene set) results in an adjusted R squared of 0.665 ( p < 0) which suggests that an important portion of the common phenotypes are similar in relevance.  The p-values were obtained through randomization of 1000 random gene sets.  Gene set 1 and gene set 2 are statistically significantly similar to each other in phenotypic terms."

Once the enrichment phenotypes of a gene set have been determined (i.e phenotypes with p < 0.05 in each gene set), it may be useful to calculate the number of these phenotypes shared between two gene sets (G and G’) to know what ratio of phenotypic terms those gene sets share.

In addition to calculating which enrichment phenotypes share two gene sets, we will be interested in determining whether this is due to the random chance. We can determine whether the Phenotypic Overlap Ratio (POR) is statistically significant by using randomization. To answer the question of whether the phenotypic overlap between G and G’ is significant. i.e. for G and G’, POR (G,G’) is compared with the POR of a random gene set POR (G,R) and POR (G’,R), where R has the same number of genes as G’ or G respectively, all genes are selected at random and all are protein coding. We can calculate the POR for different random gene sets (R1,R2,…,Rm). We can now check how many random gene sets have a higher POR than our test, if the number of higher POR of these random gene sets is less than 5% of the total then p < 0.05 and we could conclude that the number of phenotypes shared between these two gene sets is statistically significant.

Parkinson genes and Dystonia genes get a Phenotypic Overlap Ratio (POR) of 0.524 (p < 0.00999). We get a plot with the 1000 randomization values of the POR score:

comparareparkdis$POR

Not this time but sometimes POR is too demanding and valuable information cannot be obtained. In these cases it is useful Relaxed Phenotypic Overlap Ratio (RPOR). RPOR is calculated in a similar way to the POR but with all phenotypes, whether these are enriched or not.

Parkinson genes and Dystonia genes get a Relaxed Phenotypic Overlap Ratio (RPOR) of 0.473 (p < 0.00999). We get a plot with the 1000 randomization values of the RPOR score:

comparareparkdis$RPOR

We can measure the linear regression with the adjusted R square and if it is significant with the pvalue of the regression. If there is no linear relationship there is no consistent pattern of association of phenotypic relevance.

Besides measuring the phenotypic similarities between the two gene sets we can also see in which phenotypes are not similar, that is, which phenotypes make that gene set unique with respect to the other.

We get an interactive plot with the relevant phenotypic terms for each gene set:

comparareparkdis$plotdif

For example, significant only in PD phenotypes include Astrocytosis (MP:0003354), Substantia nigra gliosis (HP:0011960), Neuronal loss in central nervous system (HP:0002529) and Orthostatic hypotension due to autonomic dysfunction (HP:0004926).

  kbl(comparareparkdis$tabledif1, escape = F, digits = 1000, align = "c", format = "html", row.names = F) %>%
  kable_material_dark()
term_id term_name adjust_pvalue_set1 gene_overlap_set1 overlap_ratio_set1 pvalue_set1 common_genes_set1 adjust_pvalue_set2 gene_overlap_set2 overlap_ratio_set2 pvalue_set2 common_genes_set2
MP:0003354 astrocytosis 4.696161e-12 11 (11/159) 6.059562e-15 ATP13A2, ATP1A3, DCTN1, GBA, GRN, LRRK2, MAPT, SNCA, SPG11, TUBB4A, WDR45 0.06876015 5 (5/159) 8.426488e-05 ATP13A2, ATP1A3, TUBB4A, VAC14, WDR45
HP:0011960 Substantia nigra gliosis 4.131233e-11 6 (6/14) 6.805985e-14 FBXO7, GBA, MAPT, PRKN, LRRK2, SNCA 0.47496849 2 (2/14) 6.128626e-04 FBXO7, PRKN
HP:0002171 Gliosis 2.599204e-10 8 (8/70) 4.282049e-13 PLA2G6, CSF1R, GBA, GRN, MAPT, LRRK2, VPS35, SNCA 1.00000000 2 (2/70) 1.471849e-02 PLA2G6, YY1
HP:0002367 Visual hallucinations 3.702765e-10 6 (6/19) 6.100108e-13 FBXO7, GBA, LRRK2, VPS35, SNCA, ATP13A2 0.88454551 2 (2/19) 1.141349e-03 FBXO7, ATP13A2
MP:0008918 microgliosis 2.179921e-09 8 (8/82) 2.812801e-12 ATP1A3, CSF1R, DCTN1, GRN, LRRK2, MAPT, SLC6A3, VPS35 1.00000000 2 (2/82) 2.268157e-02 ATP1A3, SLC6A3
HP:0003677 Slow progression 6.957523e-09 9 (9/166) 1.146215e-11 FBXO7, DNAJC6, DCTN1, C19ORF12, PARK7, LRRK2, PANK2, SPG11, PINK1 0.05700405 5 (5/166) 7.355361e-05 FBXO7, C19ORF12, HPCA, PANK2, PINK1
HP:0007311 Short stepped shuffling gait 3.840002e-08 5 (5/16) 6.326198e-11 SYNJ1, DNAJC6, DCTN1, GBA, MAPT 1.00000000 1 (1/16) 4.154390e-02 SYNJ1
HP:0001621 Weak voice 1.354524e-07 5 (5/20) 2.231506e-10 SYNJ1, DNAJC6, DCTN1, GBA, MAPT 1.00000000 1 (1/20) 5.165212e-02 SYNJ1
HP:0002359 Frequent falls 1.600395e-07 7 (7/92) 2.636565e-10 C19ORF12, GBA, MAPT, LRRK2, PANK2, VPS35, SNCA 0.07826672 4 (4/92) 1.009893e-04 ADAR, C19ORF12, FA2H, PANK2
HP:0002366 Abnormal lower motor neuron morphology 2.926082e-07 5 (5/23) 4.820563e-10 DCTN1, C19ORF12, GRN, MAPT, SPG11 1.00000000 2 (2/23) 1.676591e-03 CHMP2B, C19ORF12
MP:0001262 decreased body weight 8.789076e-07 17 (17/1739) 1.134074e-09 ATP1A3, CSF1R, DNAJC6, GBA, GRN, MAPT, OPA3, PANK2, PINK1, PRKN, PRKRA, SLC30A10, SLC39A14, SLC6A3, SNCA, SPR, TH 0.07926118 14 (14/1739) 9.713380e-05 ATM, ATP1A3, ATP7B, GNAO1, HTRA2, PANK2, PINK1, PRKN, PRKRA, SLC30A10, SLC6A3, SPR, TH, TOR1A
HP:0005340 Spastic/hyperactive bladder 1.155982e-06 4 (4/10) 1.904418e-09 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
HP:0003581 Adult onset 1.913557e-06 7 (7/131) 3.152483e-09 CSF1R, DCTN1, GBA, PARK7, MAPT, PRKN, SPG11 0.30200968 4 (4/131) 3.896899e-04 CP, CHMP2B, PRKN, APTX
C0497327 Dementia 2.694854e-06 4 (4/17) 1.938744e-08 CSF1R, GRN, MAPT, SLC6A3 0.23096934 2 (2/17) 8.683058e-04 CP, SLC6A3
HP:0000012 Urinary urgency 3.708838e-06 5 (5/37) 6.110113e-09 GBA, MAPT, SPG11, SNCA, PINK1 1.00000000 2 (2/37) 4.304295e-03 FA2H, PINK1
HP:0002529 Neuronal loss in central nervous system 3.708838e-06 5 (5/37) 6.110113e-09 PLA2G6, CSF1R, GBA, GRN, MAPT 0.09847174 3 (3/37) 1.270603e-04 PLA2G6, CHMP2B, VAC14
HP:0031908 Micrographia 5.477310e-06 4 (4/14) 9.023575e-09 FTL, GBA, MAPT, SNCA 1.00000000 1 (1/14) 3.644866e-02 FTL
HP:0002375 Hypokinesia 6.336739e-06 5 (5/41) 1.043944e-08 GBA, SLC6A3, SNCA, ATP13A2, TH 0.13401312 3 (3/41) 1.729202e-04 SLC6A3, ATP13A2, TH
HP:0002120 Cerebral cortical atrophy 6.708363e-06 8 (8/249) 1.105167e-08 GBA, GRN, LRRK2, SPG11, VPS35, SNCA, VPS13A, ATP13A2 0.36796339 5 (5/249) 4.747915e-04 CHMP2B, BCAP31, FA2H, VPS13A, ATP13A2
HP:0002300 Mutism 7.181883e-06 5 (5/42) 1.183177e-08 ATP1A3, CSF1R, FTL, GRN, MAPT 0.14403143 3 (3/42) 1.858470e-04 ATP1A3, CHMP2B, FTL
HP:0000744 Low frustration tolerance 7.457898e-06 4 (4/15) 1.228649e-08 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
HP:0004926 Orthostatic hypotension due to autonomic dysfunction 9.929007e-06 4 (4/16) 1.635751e-08 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
MP:0004250 tau protein deposits 1.272881e-05 4 (4/15) 1.642427e-08 GRN, LRRK2, MAPT, PRKN 1.00000000 1 (1/15) 4.188862e-02 PRKN
MP:0002882 abnormal neuron morphology 1.733258e-05 7 (7/162) 2.236462e-08 ATP13A2, GBA, LRRK2, MAPT, PRKN, SLC6A3, SPG11 0.07504847 5 (5/162) 9.197116e-05 ATP13A2, CP, PRKN, SLC6A3, TOR1A
MP:0005405 axon degeneration 2.187874e-05 6 (6/96) 2.823063e-08 OPA3, PLA2G6, SNCA, SPG11, TUBB4A, WDR45 0.12809691 4 (4/96) 1.569815e-04 NKX6-2, PLA2G6, TUBB4A, WDR45
MP:0001473 reduced long term potentiation 2.937642e-05 7 (7/175) 3.790505e-08 GRN, MAPT, PINK1, SLC6A3, SNCA, VPS35, WDR45 1.00000000 3 (3/175) 1.323181e-02 PINK1, SLC6A3, WDR45
HP:0002145 Frontotemporal dementia 3.240804e-05 4 (4/21) 5.339051e-08 PLA2G6, DCTN1, GRN, MAPT 1.00000000 2 (2/21) 1.396636e-03 PLA2G6, CHMP2B
HP:0001824 Weight loss 4.719093e-05 7 (7/209) 7.774453e-08 DCTN1, GBA, LRRK2, PANK2, VPS35, SNCA, VPS13A 1.00000000 4 (4/209) 2.178300e-03 ATM, ATP7B, PANK2, VPS13A
HP:0002014 Diarrhea 5.714044e-05 7 (7/215) 9.413581e-08 SYNJ1, DNAJC6, PARK7, PRKN, LRRK2, SNCA, PINK1 0.18907978 5 (5/215) 2.439739e-04 SYNJ1, DDC, HTRA2, PRKN, PINK1
HP:0002465 Poor speech 5.895907e-05 7 (7/216) 9.713191e-08 CSF1R, RAB39B, TUBB4A, GRN, WDR45, MAPT, SLC39A14 0.19313478 5 (5/216) 2.492062e-04 CHMP2B, DLAT, TUBB4A, WDR45, WDR73
MP:0008842 lipofuscinosis 6.744999e-05 4 (4/22) 8.703225e-08 ATP13A2, GBA, GRN, LRRK2 1.00000000 1 (1/22) 6.082009e-02 ATP13A2
HP:0000505 Visual impairment 7.869031e-05 8 (8/344) 1.296381e-07 PLA2G6, SYNJ1, LYST, CSF1R, TUBB4A, GRN, OPA3, SPG11 1.00000000 4 (4/344) 1.220619e-02 PLA2G6, SYNJ1, MECR, TUBB4A
HP:0000514 Slow saccadic eye movements 8.034995e-05 4 (4/26) 1.323722e-07 FBXO7, MAPT, SNCA, ATP13A2 1.00000000 2 (2/26) 2.142177e-03 FBXO7, ATP13A2
MP:0004077 abnormal striatum morphology 8.188499e-05 5 (5/60) 1.056581e-07 GBA, LRRK2, PARK7, SLC6A3, SNCA 1.00000000 1 (1/60) 1.571363e-01 SLC6A3
MP:0001463 abnormal spatial learning 9.175795e-05 7 (7/207) 1.183974e-07 ATP13A2, ATP1A3, GRN, MAPT, PRKN, SLC6A3, VPS35 0.23290669 5 (5/207) 2.854249e-04 ATP13A2, ATP1A3, FA2H, PRKN, SLC6A3
C3160718 PARKINSON DISEASE, LATE-ONSET 1.545833e-04 3 (3/12) 1.112110e-06 GBA, MAPT, PRKN 1.00000000 1 (1/12) 3.058383e-02 PRKN
MP:0010069 increased serotonin level 1.869844e-04 4 (4/28) 2.412702e-07 PARK7, PRKN, SLC6A3, TH 0.05518245 3 (3/28) 6.762555e-05 PRKN, SLC6A3, TH
MP:0001263 weight loss 2.326296e-04 8 (8/358) 3.001672e-07 LYST, PARK7, PLA2G6, SLC6A3, SNCA, SPG11, TH, TUBB4A 1.00000000 5 (5/358) 3.164514e-03 PLA2G6, SLC6A3, TH, TOR1A, TUBB4A
HP:0012450 Chronic constipation 2.462922e-04 4 (4/34) 4.057532e-07 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
MP:0003172 abnormal lysosome physiology 3.262962e-04 4 (4/32) 4.210274e-07 ATP13A2, LYST, SLC6A3, SPG11 1.00000000 2 (2/32) 3.726748e-03 ATP13A2, SLC6A3
HP:0000511 Vertical supranuclear gaze palsy 3.970762e-04 3 (3/10) 6.541618e-07 DCTN1, MAPT, ATP13A2 1.00000000 1 (1/10) 2.617517e-02 ATP13A2
MP:0003633 abnormal nervous system physiology 4.167109e-04 6 (6/158) 5.376915e-07 GRN, MAPT, PINK1, SLC6A3, SNCA, TH 0.06675656 5 (5/158) 8.180951e-05 CSTB, GNAO1, PINK1, SLC6A3, TH
MP:0005404 abnormal axon morphology 8.057796e-04 6 (6/177) 1.039716e-06 LRRK2, MAPT, PLA2G6, SLC6A3, SNCA, TUBB4A 0.11336100 5 (5/177) 1.389228e-04 FA2H, PLA2G6, SLC6A3, TUBB4A, XK
HP:0000719 Inappropriate behavior 9.423931e-04 3 (3/13) 1.552542e-06 DCTN1, GRN, MAPT 1.00000000 1 (1/13) 3.389069e-02 CHMP2B
HP:0006892 Frontotemporal cerebral atrophy 9.423931e-04 3 (3/13) 1.552542e-06 PLA2G6, GRN, MAPT 0.40784816 2 (2/13) 5.262557e-04 PLA2G6, CHMP2B
HP:0008969 Leg muscle stiffness 9.423931e-04 3 (3/13) 1.552542e-06 SYNJ1, DNAJC6, ATP13A2 0.40784816 2 (2/13) 5.262557e-04 SYNJ1, ATP13A2
MP:0001906 increased dopamine level 9.994741e-04 4 (4/42) 1.289644e-06 PARK7, PRKN, SLC6A3, SNCA 1.00000000 2 (2/42) 6.346209e-03 PRKN, SLC6A3
C0752347 Lewy Body Disease 1.067389e-03 3 (3/22) 7.679058e-06 GBA, SNCA, TH 1.00000000 1 (1/22) 5.534097e-02 TH
MP:0013219 abnormal substantia nigra pars compacta morphology 1.495671e-03 3 (3/13) 1.929898e-06 PARK7, PRKN, SLC6A3 0.49606651 2 (2/13) 6.079246e-04 PRKN, SLC6A3
HP:0002186 Apraxia 1.887665e-03 4 (4/56) 3.109826e-06 PLA2G6, CSF1R, GRN, MAPT 0.33812626 3 (3/56) 4.362919e-04 PLA2G6, CHMP2B, SLC2A1
HP:0002380 Fasciculations 2.174027e-03 4 (4/58) 3.581594e-06 DCTN1, GRN, MAPT, SPG11 1.00000000 1 (1/58) 1.424249e-01 CHMP2B
MP:0011451 increased susceptibility to dopaminergic neuron neurotoxicity 2.372314e-03 3 (3/15) 3.061051e-06 GRN, PARK7, SLC6A3 1.00000000 1 (1/15) 4.188862e-02 SLC6A3
C0751263 Learning Disturbance 2.508527e-03 3 (3/29) 1.804695e-05 MAPT, PRKN, TH 0.67518493 2 (2/29) 2.538289e-03 PRKN, TH
C0751265 Learning Disabilities 2.508527e-03 3 (3/29) 1.804695e-05 MAPT, PRKN, TH 0.67518493 2 (2/29) 2.538289e-03 PRKN, TH
HP:0003587 Insidious onset 2.670015e-03 3 (3/18) 4.398706e-06 GBA, MAPT, SNCA 1.00000000 0 1 1.000000e+00 1
HP:0100753 Schizophrenia 3.433314e-03 4 (4/65) 5.656201e-06 GBA, LRRK2, VPS35, SNCA 1.00000000 0 1 1.000000e+00 1
C0005586 Bipolar Disorder 3.465428e-03 7 (7/518) 2.493114e-05 ATP1A3, GCH1, GRN, SLC6A3, SPR, TH, PLA2G6 0.08020531 7 (7/518) 3.015237e-04 ATP1A3, DDC, GCH1, SLC6A3, SPR, TH, PLA2G6
MP:0005059 lysosomal protein accumulation 3.534768e-03 3 (3/17) 4.560991e-06 ATP13A2, DCTN1, LYST 1.00000000 1 (1/17) 4.733698e-02 ATP13A2
MP:0010149 abnormal synaptic dopamine release 3.534768e-03 3 (3/17) 4.560991e-06 LRRK2, SLC6A3, SNCA 1.00000000 1 (1/17) 4.733698e-02 SLC6A3
HP:0002185 Neurofibrillary tangles 4.333617e-03 3 (3/21) 7.139403e-06 PLA2G6, GRN, MAPT 1.00000000 1 (1/21) 5.416215e-02 PLA2G6
HP:0000011 Neurogenic bladder 5.754420e-03 3 (3/23) 9.480098e-06 FBXO7, SNCA, ATP13A2 1.00000000 2 (2/23) 1.676591e-03 FBXO7, ATP13A2
MP:0000160 kyphosis 6.481472e-03 6 (6/255) 8.363189e-06 GBA, PINK1, PLA2G6, PRKN, SLC6A3, SNCA 1.00000000 4 (4/255) 5.668553e-03 PINK1, PLA2G6, PRKN, SLC6A3
MP:0010047 axonal spheroids 6.872063e-03 3 (3/21) 8.867178e-06 CSF1R, PLA2G6, WDR45 1.00000000 2 (2/21) 1.611633e-03 PLA2G6, WDR45
C0025261 Memory Disorders 8.312055e-03 3 (3/43) 5.979896e-05 MAPT, PRKN, SLC6A3 1.00000000 2 (2/43) 5.509350e-03 PRKN, SLC6A3
MP:0003461 abnormal response to novel object 8.755837e-03 4 (4/72) 1.129785e-05 ATP13A2, ATP1A3, GRN, SLC6A3 0.91344756 3 (3/72) 1.119421e-03 ATP13A2, ATP1A3, SLC6A3
MP:0000753 paralysis 9.761519e-03 4 (4/74) 1.259551e-05 ATP1A3, DCTN1, GBA, PRKRA 0.98858135 3 (3/74) 1.211497e-03 ATP1A3, HTRA2, PRKRA
HP:0000709 Psychosis 1.043788e-02 4 (4/86) 1.719585e-05 GRN, MAPT, PANK2, VPS13A 0.06025076 4 (4/86) 7.774292e-05 CHMP2B, PANK2, DCAF17, VPS13A
MP:0008260 abnormal autophagy 1.084961e-02 4 (4/76) 1.399949e-05 LRRK2, PRKN, SLC6A3, SPG11 1.00000000 2 (2/76) 1.968749e-02 PRKN, SLC6A3
C0011570 Mental Depression 1.176826e-02 5 (5/260) 8.466377e-05 ATP1A3, GRN, SLC6A3, SNCA, TH 0.13757837 5 (5/260) 5.172119e-04 ADCY5, ATP1A3, SLC6A3, TH, SGCE
MP:0011448 decreased dopaminergic neuron number 1.181268e-02 3 (3/25) 1.524216e-05 PRKN, SLC6A3, SNCA 1.00000000 2 (2/25) 2.284651e-03 PRKN, SLC6A3
MP:0004811 abnormal neuron physiology 1.354081e-02 5 (5/169) 1.747201e-05 ATP1A3, GRN, PINK1, SLC6A3, SNCA 1.00000000 4 (4/169) 1.311801e-03 ATP1A3, PINK1, SLC6A3, TOR1A
MP:0001399 hyperactivity 1.399495e-02 8 (8/631) 1.805800e-05 ATP1A3, LRRK2, MAPT, PLA2G6, SLC6A3, SNCA, TH, WDR45 0.24682723 8 (8/631) 3.024843e-04 ATP1A3, CSTB, GNAO1, PLA2G6, SLC6A3, TH, TOR1A, WDR45
HP:0002344 Progressive neurologic deterioration 1.444282e-02 3 (3/31) 2.379378e-05 SYNJ1, GBA, GCH1 1.00000000 2 (2/31) 3.037653e-03 SYNJ1, GCH1
HP:0002483 Bulbar signs 1.591464e-02 3 (3/32) 2.621852e-05 GBA, SPG11, SLC39A14 1.00000000 1 (1/32) 8.132950e-02 CHMP2B
C0011206 Delirium 1.894869e-02 2 (2/10) 1.363215e-04 SLC6A3, TH 0.07736782 2 (2/10) 2.908565e-04 SLC6A3, TH
MP:0009454 impaired contextual conditioning behavior 2.403030e-02 4 (4/93) 3.100684e-05 ATP1A3, GRN, MAPT, WDR45 1.00000000 2 (2/93) 2.861596e-02 ATP1A3, WDR45
MP:0004768 abnormal axonal transport 2.520749e-02 3 (3/32) 3.252579e-05 MAPT, PRKN, SLC6A3 1.00000000 2 (2/32) 3.726748e-03 PRKN, SLC6A3
MP:0001732 postnatal growth retardation 2.554289e-02 9 (9/915) 3.295856e-05 CSF1R, MAPT, OPA3, PANK2, PRKRA, SLC39A14, SLC6A3, SPR, SYNJ1 0.57656057 9 (9/915) 7.065693e-04 ATM, ATP7B, DDC, HTRA2, PANK2, PRKRA, SLC6A3, SPR, SYNJ1
HP:0002354 Memory impairment 2.642845e-02 4 (4/109) 4.353946e-05 CSF1R, GRN, MAPT, VPS13A 0.15027673 4 (4/109) 1.939055e-04 CP, CHMP2B, PRRT2, VPS13A
MP:0008571 abnormal synaptic bouton morphology 2.768659e-02 3 (3/33) 3.572463e-05 MAPT, PLA2G6, SLC6A3 1.00000000 2 (2/33) 3.959565e-03 PLA2G6, SLC6A3
C0030569 Secondary Parkinson Disease 2.772393e-02 2 (2/12) 1.994528e-04 PRKN, ATP13A2 0.11307517 2 (2/12) 4.250946e-04 PRKN, ATP13A2
C0751414 Parkinson Disease, Secondary Vascular 2.772393e-02 2 (2/12) 1.994528e-04 PRKN, ATP13A2 0.11307517 2 (2/12) 4.250946e-04 PRKN, ATP13A2
C0751415 Atherosclerotic Parkinsonism 2.772393e-02 2 (2/12) 1.994528e-04 PRKN, ATP13A2 0.11307517 2 (2/12) 4.250946e-04 PRKN, ATP13A2
MP:0002062 abnormal associative learning 3.311306e-02 3 (3/35) 4.272653e-05 MAPT, SLC6A3, TH 1.00000000 2 (2/35) 4.444897e-03 SLC6A3, TH
HP:0010526 Dysgraphia 3.377625e-02 3 (3/41) 5.564456e-05 GRN, MAPT, VPS13A 1.00000000 2 (2/41) 5.261879e-03 CHMP2B, VPS13A
C0036341 Schizophrenia 3.448579e-02 8 (8/1026) 2.480992e-04 GCH1, GRN, SLC6A3, PLA2G6, VPS35, PINK1, PANK2, LRRK2 0.21177909 9 (9/1026) 7.961620e-04 ATM, CP, DDC, GCH1, GNAO1, SLC6A3, PLA2G6, PINK1, PANK2
HP:0000666 Horizontal nystagmus 3.632367e-02 3 (3/42) 5.984130e-05 GBA, GCH1, ATP13A2 0.14403143 3 (3/42) 1.858470e-04 GCH1, FA2H, ATP13A2
HP:0002518 Abnormality of the periventricular white matter 3.899347e-02 3 (3/43) 6.423966e-05 CSF1R, SPG11, ATP13A2 1.00000000 2 (2/43) 5.773851e-03 FA2H, ATP13A2
C0013386 Dyskinesia, Drug-Induced 4.394579e-02 2 (2/15) 3.161568e-04 GCH1, TH 0.17894818 2 (2/15) 6.727375e-04 GCH1, TH

On the other hand, we found significant only phenotypes in EOD such as Writer’s cramp (HP:0002356), Hypoplasia of the corpus callosum (HP:0002079), Acanthocytosis (HP:0001927), Microcephaly (HP:0000252), Intellectual disability, mild (HP:0001256) and Hyperactive deep tendon reflexes (HP:0006801).

  kbl(comparareparkdis$tabledif2, escape = F, digits = 1000, align = "c", format = "html", row.names = F) %>%
  kable_material_dark()
term_id term_name adjust_pvalue_set1 gene_overlap_set1 overlap_ratio_set1 pvalue_set1 common_genes_set1 adjust_pvalue_set2 gene_overlap_set2 overlap_ratio_set2 pvalue_set2 common_genes_set2
HP:0002356 Writer’s cramp 0.22988089 2 (2/16) 3.787165e-04 FTL, GCH1 1.544582e-09 6 (6/16) 1.993010e-12 SGCE, TOR1A, FTL, GCH1, PRRT2, THAP1
HP:0002355 Difficulty walking 0.47371937 4 (4/233) 7.804273e-04 SYNJ1, C19ORF12, SLC30A10, ATP13A2 1.371032e-08 11 (11/233) 1.769073e-11 ADAR, ADCY5, ATP7B, SYNJ1, C19ORF12, NKX6-2, HPCA, FA2H, SLC30A10, COASY, ATP13A2
HP:0003593 Infantile onset 0.07185941 6 (6/444) 1.183845e-04 PLA2G6, GCH1, SLC6A3, SPR, TH, PINK1 5.538158e-08 13 (13/444) 7.146011e-11 ADAR, PLA2G6, PNKD, DDC, DLAT, NKX6-2, GCH1, WDR73, SLC2A1, SLC6A3, SPR, TH, PINK1
HP:0003829 Incomplete penetrance 1.00000000 2 (2/147) 2.883347e-02 ATP1A3, LRRK2 3.368622e-06 8 (8/147) 4.346610e-09 ATP1A3, SGCE, KMT2B, TOR1A, PRRT2, THAP1, SLC2A1, ANO3
HP:0002487 Hyperkinetic movements 0.61490335 2 (2/26) 1.013020e-03 GCH1, SLC6A3 5.184152e-06 5 (5/26) 6.689229e-09 PNKD, GCH1, GNAO1, PRRT2, SLC6A3
HP:0000722 Obsessive-compulsive behavior 1.00000000 2 (2/61) 5.462303e-03 GCH1, PANK2 9.652139e-06 6 (6/61) 1.245437e-08 SGCE, TOR1A, GCH1, PANK2, COASY, XK
HP:0002079 Hypoplasia of the corpus callosum 1.00000000 3 (3/385) 3.081831e-02 SYNJ1, SPG11, ATP13A2 3.621692e-05 10 (10/385) 4.673150e-08 ADAR, SYNJ1, NKX6-2, GNAO1, HTRA2, WDR73, FA2H, COASY, ATP13A2, YY1
HP:0002059 Cerebral atrophy 0.11466134 5 (5/302) 1.888984e-04 PLA2G6, SYNJ1, GBA, WDR45, SLC39A14 5.935410e-05 9 (9/302) 7.658594e-08 PLA2G6, SYNJ1, BCAP31, NKX6-2, GNAO1, HTRA2, WDR45, WDR73, SLC2A1
HP:0001270 Motor delay 0.05402004 6 (6/421) 8.899512e-05 PRKRA, ATP1A3, TUBB4A, GBA, SPR, TH 8.206003e-05 10 (10/421) 1.058839e-07 ADCY5, PRKRA, ATP1A3, KMT2B, MECR, TUBB4A, NKX6-2, WDR73, SPR, TH
HP:0000252 Microcephaly 1.00000000 5 (5/939) 2.195749e-02 SYNJ1, TUBB4A, GBA, SLC30A10, SPR 3.127271e-04 13 (13/939) 4.035188e-07 ADAR, SYNJ1, KMT2B, DLAT, BCAP31, TUBB4A, GNAO1, WDR73, SERAC1, SLC30A10, SLC2A1, COASY, SPR
MP:0002183 gliosis 0.05681233 4 (4/116) 7.330623e-05 ATP13A2, SNCA, TH, VPS13A 7.270068e-04 6 (6/116) 8.909397e-07 ATP13A2, HTRA2, TH, TOR1A, VAC14, VPS13A
C0041696 Unipolar Depression 0.17968390 4 (4/274) 1.292690e-03 FTL, GCH1, TH, PINK1 1.545696e-03 7 (7/274) 5.810888e-06 ADCY5, ATP7B, DDC, FTL, GCH1, TH, PINK1
HP:0011968 Feeding difficulties 0.08093255 6 (6/454) 1.333320e-04 PLA2G6, SYNJ1, GBA, SLC6A3, VPS13A, TH 1.690898e-03 9 (9/454) 2.181804e-06 PLA2G6, SYNJ1, WDR73, SERAC1, HPCA, SLC6A3, VPS13A, TH, YY1
MP:0003908 decreased stereotypic behavior 0.12819361 2 (2/10) 1.654111e-04 PINK1, TH 2.102033e-03 3 (3/10) 2.576021e-06 PINK1, SGCE, TH
HP:0002307 Drooling 0.33657540 3 (3/89) 5.544900e-04 ATP1A3, RAB39B, VPS13A 2.840632e-03 5 (5/89) 3.665332e-06 ATP1A3, ATP7B, DLAT, VAC14, VPS13A
MP:0002204 abnormal neurotransmitter level 0.15647134 2 (2/11) 2.018985e-04 SPR, VPS13A 2.884006e-03 3 (3/11) 3.534321e-06 DDC, SPR, VPS13A
HP:0001927 Acanthocytosis 0.12706553 2 (2/12) 2.093337e-04 PANK2, VPS13A 2.932568e-03 3 (3/12) 3.783958e-06 PANK2, VPS13A, XK
HP:0003621 Juvenile onset 1.00000000 2 (2/94) 1.252821e-02 PANK2, SPG11 3.714853e-03 5 (5/94) 4.793359e-06 ADCY5, SGCE, HPCA, APTX, PANK2
HP:0045084 Limb myoclonus 1.00000000 1 (1/14) 2.514880e-02 MAPT 4.832461e-03 3 (3/14) 6.235433e-06 SGCE, TOR1A, SLC2A1
HP:0012075 Personality disorder 1.00000000 0 1 1.000000e+00 1 4.832461e-03 3 (3/14) 6.235433e-06 SGCE, TOR1A, XK
HP:0001256 Intellectual disability, mild 1.00000000 1 (1/271) 3.872335e-01 TH 4.900096e-03 7 (7/271) 6.322705e-06 ADAR, DLAT, PRRT2, DCAF17, SLC2A1, TH, YY1
HP:0002061 Lower limb spasticity 1.00000000 2 (2/48) 3.421411e-03 FBXO7, SPG11 5.989559e-03 4 (4/48) 7.728464e-06 FBXO7, FA2H, PRRT2, SLC2A1
HP:0002078 Truncal ataxia 1.00000000 2 (2/48) 3.421411e-03 ATP1A3, SLC30A10 5.989559e-03 4 (4/48) 7.728464e-06 ATP1A3, NKX6-2, APTX, SLC30A10
HP:0025401 Staring gaze 1.00000000 1 (1/15) 2.692006e-02 SYNJ1 6.028363e-03 3 (3/15) 7.778533e-06 SYNJ1, PNKD, PRRT2
HP:0000486 Strabismus 1.00000000 5 (5/696) 6.955770e-03 PLA2G6, LYST, RAB39B, GBA, ATP13A2 6.812392e-03 10 (10/696) 8.790184e-06 PLA2G6, ATM, BCAP31, NKX6-2, GNAO1, WDR73, FA2H, SLC2A1, ATP13A2, YY1
C0020796 Profound Mental Retardation 0.25904590 3 (3/139) 1.863640e-03 TH, PRKRA, RAB39B 7.535602e-03 5 (5/139) 2.832933e-05 SLC2A1, TH, YY1, PRKRA, PRRT2
C0917816 Mental deficiency 0.25904590 3 (3/139) 1.863640e-03 TH, PRKRA, RAB39B 7.535602e-03 5 (5/139) 2.832933e-05 SLC2A1, TH, YY1, PRKRA, PRRT2
MP:0001409 increased stereotypic behavior 1.00000000 2 (2/51) 4.437211e-03 SLC6A3, TH 1.068880e-02 4 (4/51) 1.309902e-05 HTRA2, SLC6A3, TH, TOR1A
HP:0003324 Generalized muscle weakness 0.75994169 3 (3/118) 1.251963e-03 PLA2G6, DCTN1, ATP13A2 1.122436e-02 5 (5/118) 1.448304e-05 PLA2G6, PNKD, CHMP2B, PRRT2, ATP13A2
HP:0001290 Generalized hypotonia 1.00000000 6 (6/933) 4.938328e-03 PLA2G6, ATP1A3, SYNJ1, CSF1R, C19ORF12, TH 1.310906e-02 11 (11/933) 1.691492e-05 PLA2G6, ATP1A3, SYNJ1, SGCE, C19ORF12, TOR1A, NKX6-2, GNAO1, HTRA2, SERAC1, TH
C1269683 Major Depressive Disorder 1.00000000 3 (3/265) 1.102997e-02 GCH1, TH, PINK1 1.491246e-02 6 (6/265) 5.606188e-05 ADCY5, ATP7B, DDC, GCH1, TH, PINK1
MP:0003964 abnormal noradrenaline level 0.48130287 2 (2/19) 6.210360e-04 SLC6A3, TH 1.664463e-02 3 (3/19) 2.039783e-05 DDC, SLC6A3, TH
HP:0001344 Absent speech 1.00000000 2 (2/227) 6.260130e-02 WDR45, SLC6A3 2.114042e-02 6 (6/227) 2.727796e-05 GNAO1, WDR45, SERAC1, SLC2A1, SLC6A3, YY1
CRB:XXX No CRB phenotype 0.05369845 23 (23/12797) 1.789948e-03 ATP13A2, C19orf12, CSF1R, FTL, GBA, GCH1, LYST, PANK2, PARK7, PINK1, PLA2G6, PRKN, PRKRA, PTRHD1, RAB39B, SLC6A3, SLC30A10, SLC39A14, SNCA, SPG11, SPR, SYNJ1, TH 2.599065e-02 32 (32/12797) 8.122079e-04 ADAR, ANO3, APTX, ATM, ATP7B, ATP13A2, C19orf12, CHMP2B, CP, DDC, FA2H, FTL, GCH1, GNAO1, HTRA2, NKX6-2, PANK2, PINK1, PLA2G6, PNKD, PRKN, PRKRA, SERAC1, SGCE, SLC6A3, SLC30A10, SPR, SYNJ1, TH, TOR1A, VAC14, XK
MP:0002804 abnormal motor learning 1.00000000 2 (2/64) 6.896078e-03 MAPT, PARK7 2.637289e-02 4 (4/64) 3.231972e-05 ATM, DDC, FA2H, SGCE
HP:0007002 Motor axonal neuropathy 1.00000000 1 (1/25) 4.445165e-02 C19ORF12 2.986310e-02 3 (3/25) 3.853303e-05 C19ORF12, COASY, XK
HP:0002131 Episodic ataxia 1.00000000 1 (1/26) 4.618685e-02 ATP1A3 3.369017e-02 3 (3/26) 4.347119e-05 ATP1A3, GNAO1, SLC2A1
MP:0002690 akinesia 0.90624072 2 (2/26) 1.169343e-03 GBA, TH 4.398621e-02 3 (3/26) 5.390467e-05 DDC, HTRA2, TH 
prueba <- comparareparkdis$tabledif2